Gao Ming, Guo Ning, Huang Chuanshu, Song Lun
Department of Cellular Immunology, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, P. R. China.
Curr Protein Pept Sci. 2009 Aug;10(4):388-94. doi: 10.2174/138920309788922216.
Mammalian cells are prone to tumorigenesis when suffering the genotoxic stresses, and the existence of the tumor suppressors validly decrease this possibility. Gadd45alpha is one of the growth arrest and DNA damage-inducible (Gadd) 45 gene family members and serves as a stress sensor and tumor suppressor under most stress conditions, which is evidenced by cell cycle arrest, DNA repair, senescence or apoptosis triggered by induction of GADD45alpha expression. However, some recent reports have challenged this notion by demonstrating the correlation of GADD45alpha expression to cell survival and even progression of certain tumor cells. Therefore, GADD45alpha seems to exert multiple roles in stress signaling and tumor development. Elucidation of the related mechanisms will be helpful for the establishment of novel tumor therapeutic strategy targeting GADD45alpha.
哺乳动物细胞在遭受基因毒性应激时容易发生肿瘤形成，而肿瘤抑制因子的存在有效地降低了这种可能性。Gadd45α是生长停滞和DNA损伤诱导（Gadd）45基因家族成员之一，在大多数应激条件下作为应激传感器和肿瘤抑制因子，这一点通过诱导GADD45α表达引发的细胞周期停滞、DNA修复、衰老或凋亡得到证明。然而，最近的一些报告对这一观点提出了挑战，这些报告表明GADD45α表达与某些肿瘤细胞的存活甚至进展相关。因此，GADD45α似乎在应激信号传导和肿瘤发展中发挥多种作用。阐明相关机制将有助于建立针对GADD45α的新型肿瘤治疗策略。
